The goal of the proposed work is to develop a chemotherapeutic procedure for selective inactivation of mammalian cells based on differences in lengths of phases of the mitotic cycle. The chemotherapeutic procedure is initially being tested with cells growing in vitro possessing various intermitotic times and various lengths of S phases. The procedure involved: 1) application of low concentrations of inhibitors of DNA synthesis (hydroxyurea or arabinosylcytosine), 2) release of the inhibition for various lengths of time, 3) readdition of the inhibitor, 4) release of the inhibition,..., for extended periods of time. We propose to show that the effect of this program on cell viability is determined by the relationship between the length of the S phase of a given cell population and the length of the release of the inhibition of DNA synthesis. When the release of the inhibition is equal to, or longer than, the S phase, the cells survive the treatment and continue to grow. When the release of the period of inhibition is shorter than the S phase, the cells are inactivated, presumably due to unbalanced growth, when lower concentrations of the inhibitors are employed. The program is being tested with HeLa, KB, L1210, L929 and CHO cells grown in spinner cultures. When these cultures are treated with the program, we anticipate finding that cultures with average lengths of S phases longer than the length of the release period will become non-viable and cells with shorter S phases will survive.